Role of Epigenetics in Inflammation-Associated Diseases
- 28 June 2012
- book chapter
- review article
- Published by Springer Science and Business Media LLC
- Vol. 61, 627-657
- https://doi.org/10.1007/978-94-007-4525-4_27
Abstract
There is considerable evidence suggesting that epigenetic mechanisms may mediate development of chronic inflammation by modulating the expression of pro-inflammatory cytokine TNF-α, interleukins, tumor suppressor genes, oncogenes and autocrine and paracrine activation of the transcription factor NF-κB. These molecules are constitutively produced by a variety of cells under chronic inflammatory conditions, which in turn leads to the development of major diseases such as autoimmune disorders, chronic obstructive pulmonary diseases, neurodegenerative diseases and cancer. Distinct or global changes in the epigenetic landscape are hallmarks of chronic inflammation driven diseases. Epigenetics include changes to distinct markers on the genome and associated cellular transcriptional machinery that are copied during cell division (mitosis and meiosis). These changes appear for a short span of time and they necessarily do not make permanent changes to the primary DNA sequence itself. However, the most frequently observed epigenetic changes include aberrant DNA methylation, and histone acetylation and deacetylation. In this chapter, we focus on pro-inflammatory molecules that are regulated by enzymes involved in epigenetic modifications such as arginine and lysine methyl transferases, DNA methyltransferase, histone acetyltransferases and histone deacetylases and their role in inflammation driven diseases. Agents that modulate or inhibit these epigenetic modifications, such as HAT or HDAC inhibitors have shown great potential in inhibiting the progression of these diseases. Given the plasticity of these epigenetic changes and their readiness to respond to intervention by small molecule inhibitors, there is a tremendous potential for the development of novel therapeutics that will serve as direct or adjuvant therapeutic compounds in the treatment of these diseases.Keywords
This publication has 101 references indexed in Scilit:
- Cancer chemoprevention by dietary polyphenols: Promising role for epigeneticsBiochemical Pharmacology, 2010
- Histone deacetylase (HDAC) inhibitors in recent clinical trials for cancer therapyClinical Epigenetics, 2010
- Inflammation and oncogenesis: a vicious connectionCurrent Opinion in Genetics & Development, 2009
- Non-CpG Methylation of the PGC-1α Promoter through DNMT3B Controls Mitochondrial DensityCell Metabolism, 2009
- Current concepts on the role of inflammation in COPD and lung cancerCurrent Opinion in Pharmacology, 2009
- Inflammation and cancer: how friendly is the relationship for cancer patients?Current Opinion in Pharmacology, 2009
- Histone deacetylase inhibitors: Potential in cancer therapyJournal of Cellular Biochemistry, 2009
- Inflammation and cancer: The oncogene-driven connectionCancer Letters, 2008
- Modulation of p53 Function by SET8-Mediated Methylation at Lysine 382Molecular Cell, 2007
- Histone Demethylation Mediated by the Nuclear Amine Oxidase Homolog LSD1Cell, 2004